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How to improve motor learning in Drosophila

Motor learning, skill-learning or habit formation share conceptual similarities, but it is debated how much biology these processes have in common. There is genetic evidence linking motor learning and habit formation in flies, song-learning in birds and language acquisition in humans to an evolutionary conserved operant self-learning process. The FoxP transcription factor family as well the protein kinase C (PKC) family of genes are involved in all of these phenomena. Here we show different biological manipulations of Drosophila that all enhance motor learning. Mutations in genes involved in classical conditioning, such as rutabaga or radish, enhance motor learning (while decreasing or abolishing classical learning).Overexpression of an operant learning gene, atypical PKC (aPKC) enhances motor learning as well as habit formation. Inhibition of a prominent interaction partner of aPKC, bazooka, also enhances motor learning. Inhibition of a prominent insect neuropil, the mushroom-bodies (MBs) has been previously reported to enhance habit formation such that premature habits are formed. We show here that this function is mediated via MB output neuron 2 (MBON-02, aka. MBON-β2β'2a). The anatomy of this neuron indicates that non-olfactory MB Kenyon cells of the β2 and β’2-lobes are involved in this enhancement. These neurons receive input via their dendrites in the little-studied lateral (lACA) and dorsal (dACA) accessory calyx regions of the MB. Our preliminary data suggest that thermosensory input from the lACA and visual input from the dACA are both simultaneously necessary for the inhibition of premature habits. However, they are separately sufficient to trigger the inhibition via MBON-02. We will also show data comparing the motor learning efficacy of rover and sitter flies, which carry different variants of the protein kinase G (PKG) gene. Given the conserved nature of these learning processes in all bilaterian animals including humans and the role of motor learning in language acquisition, habit formation/addiction and rehabilitation after stroke or spinal cord injury, the diversity of these learning enhancements promises a rich field for the development of medical applications.